Brams P, Nguyen M L, Chamat S, Royston I, Morrow P R
IDEC Pharmaceuticals Corporation, San Diego, CA 92121, USA.
J Immunol. 1998 Mar 1;160(5):2051-8.
High titers of Ag-specific human IgG were consistently achieved in SCID mice reconstituted with human splenocytes that had been primed with Ag in vitro and then boosted with Ag after engraftment into SCID mice. Specific human IgG titers in the hu-SPL-SCID mice reached approximately 1:4 x 10(5) when the mice were immunized with a neo-antigen, whereas titers reached 1:2 x 10(6) when recall responses were induced. Booster immunizations with Ag 21 days after the initial in vivo boost further enhanced this response, and specific human IgG titers of 1:17 x 10(6) were achieved. This represented an essentially monospecific IgG population. These responses were CD4+ T cell dependent. In addition, affinity maturation of the human Ab responses was observed. Spleens of hu-SPL-SCID mice with Ag-specific titers < or = 1:1 x 10(6) were often significantly enlarged and often displayed visible tumors. Fourteen of sixteen B cell tumors removed from spleens of five such hu-SPL-SCID mice, produced Abs that were specific for the immunizing Ags. From such tumor, cloned cell lines were established. One such mAb, MLN-7 (gamma1, kappa), was raised to tetanus toxoid and had no identified cross-reactivity.
在用人脾细胞重建的SCID小鼠中，始终能获得高滴度的抗原特异性人IgG。这些人脾细胞先在体外经抗原致敏，然后植入SCID小鼠后再用抗原进行加强免疫。当用新抗原免疫hu-SPL-SCID小鼠时，其特异性人IgG滴度达到约1:4×10⁵，而诱导回忆反应时滴度达到1:2×10⁶。在初次体内加强免疫21天后用抗原进行加强免疫进一步增强了这种反应，特异性人IgG滴度达到1:17×10⁶。这代表了一个基本为单特异性的IgG群体。这些反应依赖于CD4⁺T细胞。此外，还观察到了人抗体反应的亲和力成熟。抗原特异性滴度≤1:1×10⁶的hu-SPL-SCID小鼠的脾脏常常明显肿大，且常常可见肿瘤。从五只此类hu-SPL-SCID小鼠的脾脏中切除的16个B细胞肿瘤中，有14个产生了针对免疫抗原的抗体。从这样的肿瘤中建立了克隆细胞系。一种这样的单克隆抗体MLN-7（γ1，κ）是针对破伤风类毒素产生的，未发现有交叉反应。
